Photolyase and cryptochrome are evolutionarily and structurally related flavoenzymes that catalyze two entirely different biological reactions. Photolyase is an enzyme that uses the energy of blue light to reverse UV-induced DNA photoproducts and thus prevents the mutagenic and lethal effects of UV. Cryptochrome regulates the circadian clock in animals, growth and development in plants, and performs an unknown function in bacteria. The basic photochemical reaction carried out by photolyase is relatively well understood but the photocatalytic function of cryptochrome is not known. The goal of this research is to understand how photolyase and cryptochrome perform their distinct functions. Towards this aim, the following experiments will be conducted. 1. We will characterize the photoreceptor function and the functional dynamics of the excited states of the photolyase/cryptochrome family by ultrafast spectroscopy. 2. We will investigate the mechanisms of signal transduction of animal, plant and microbial cryptochromes. 3. We will analyze the light-independent function of cryptochrome in the circadian clock and determine the effects of clock disruption on DNA damage checkpoints at the cellular level and on tumorigenesis in mice.